Our hypothesis is that fundamental opiate signaling processes evolved in invertebrate neural tissues and has been evolutionarily retained in humans. This contention is supported by our findings that invertebrate's produce endogenous morphine and have m3 opiate receptors, which are indistinguishable from the human counterpart. The experiments in this proposal are designed to examine the presence of morphine and m3 receptors in the invertebrate nervous system and directly related these findings to humans. We propose to address the following objectives: What is the role of the opiate alkaloid, i.e., morphine, in the invertebrate nervous system and what does it tell us about the human system? The experiments in this proposal are designed to answer these questions. More specifically, these studies test our hypothesis that opiate signaling evolved in invertebrates to diminish sensory inputs and anti- inflammatory processes and that because this system worked so well, it was retained in during evolution. Given this growing documentation for morphine signaling in invertebrates and vertebrates, it is important to demonstrate both the presence of morphine and its associated r4eceptor, m3 and how this presence is modulated. Our objectives are: 1) Clone the mu3 receptor gene from invertebrate ganglia, 2) Study the invertebrate ganglia mu3 receptor gene and protein expression, 3) Characterize morphine stimulated intracellular transduction mechanisms, i.e., nitric oxide and calcium transients. Examine the interaction between morphine and its metabolites with mu3 opiate receptor expression as well as determine in the animal in which tissues, besides nervous, this relationship occurs, 4) Develop an invertebrate, i.e., alternate animal, for understanding naturally occurring morphine processes. This will also provide for a linkage with the parasite-behavior project in that both will address the presence of an endogenous opiate system. It will also fit in nicely with the 2 new faculties that will be developing their expertise in a new scientific area of endeavor that promises to impact on mental health from a neuroscience perspective, and 5) involve undergraduate minority students in this research, thus developing a strong interest in mental health.